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J Control Release. 2018 Jun 28;280:99-112. doi: 10.1016/j.jconrel.2018.05.004. Epub 2018 May 7.

In vivo inhibition of circulating tumor cells by two apoptosis-promoting circular aptamers with enhanced specificity.

Author information

1
Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350116, China; Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian 350108, China.
2
Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350116, China.
3
School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China.
4
Oncology Department, Fuzhou General Hospital, 156 Western Two-Circle North Road, Fuzhou, Fujian 350025, China.
5
Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350116, China. Electronic address: cmapcjia1234@163.com.

Abstract

Circulating tumor cells (CTCs) are known as the root cause of cancer metastasis that accounts for 90% of cancer death. Owing to the rarity of blood CTCs and their microenvironmental complexity, the existing biotechnology could not precisely capture and apoptosize CTCs in vivo for cancer metastasis prevention. Here, we designed two double strand circular aptamers aimed to simultaneously target MUC1 and HER2 surface biomarkers on mesenchymal cancer cells. The circular aptamers are composed of a capture arm for binding and seizing CTCs and a circular body for resisting degradation by exonucleases. We conjugated the two circular aptamers onto dendrimer PAMAM G4.5 (dcAp1-G-dcAp2), and the conjugate entity showed both significantly-enhanced biostability in serum for days compared with their linear counterparts and capture specificity in RBC (1:108) compared with their single circular aptamers. dcAp1-G-dcAp2 apoptosized the targeted cells and inhibited their bioenergetic activities significantly by lowing △Ψm, ATP and lactate productions while increasing ROS production. dcAp1-G-dcAp2 captured CTCs in mice in vivo and in patient blood. This study lays the foundation for developing multiple biostable circular aptamers and conjugating them together to precisely capture and apoptosize mesenchymal CTCs in vivo.

KEYWORDS:

Apoptosis-promoting; Biostability; Circular aptamer; Circulating tumor cells; in vivo inhibition

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